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Cellular Oncology
Published in: Cellular Oncology 6/2015

01-12-2015 | Original Paper

The carboxy-terminal domain of connexin 43 (CT-Cx43) modulates the expression of p53 by altering miR-125b expression in low-grade human breast cancers

Authors: Raihana Maqbool, Rabiya Rashid, Rehana Ismail, Saif Niaz, Nisar Ahmad Chowdri, Mahboob Ul Hussain

Published in: Cellular Oncology | Issue 6/2015

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Abstract

Purpose

Connexin 43 (Cx43) is a widely expressed gap junction protein. It can also regulate various gap-junction independent processes, including cellular proliferation. The latter regulatory functions have been attributed to its carboxy-terminal domain, CT-Cx43. CT-Cx43 has been found to be expressed independent of full-length Cx43 in various cell types. Its nuclear localization has additionally raised the possibility that it may regulate the expression of particular genes, including miRNAs, known play a role in the regulation of cellular proliferation. Here, we set out to uncover the molecular mechanism(s) underlying CT-Cx43 mediated gene (de-)regulation in human breast cancer.

Methods

Western blotting and quantitative real time PCR were carried to assess the expression of CT-Cx43 and miR-125b in a panel of 60 primary human breast cancer tissues and its paired normal adjacent tissues. In addition, CT-Cx43 was exogenously expressed in the breast cancer-derived cell line MCF-7 and its effect on the expression of miR-125b and its downstream target p53 were evaluated, as well as its effect on cellular proliferation and death using MTT and LDH assays, respectively.

Results

We found that CT-Cx43, but not full-length Cx43, was down-regulated in low grade human breast cancers. In addition, we found that the tumor suppressor protein p53 exhibited a decreased expression in the CT-Cx43 down-regulated samples. Interestingly, we found that miR-125b, a negative regulator of p53, exhibited an inverse expression relationship with CT-Cx43 in the breast cancer samples tested. This inverse relationship was confirmed by exogenous expression of CT-Cx43 in MCF-7 cells. In addition, we found that CT-Cx43 up-regulation and subsequent miR-125b down-regulation resulted in a decreased proliferation of MCF-7 cells.

Conclusions

Our data suggest a mechanism by which CT-Cx43 may regulate cell proliferation. Targeting of CT-Cx43 and/or miR-125b may be instrumental for therapeutic intervention in human breast cancer.
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Metadata
Title
The carboxy-terminal domain of connexin 43 (CT-Cx43) modulates the expression of p53 by altering miR-125b expression in low-grade human breast cancers
Authors
Raihana Maqbool
Rabiya Rashid
Rehana Ismail
Saif Niaz
Nisar Ahmad Chowdri
Mahboob Ul Hussain
Publication date
01-12-2015
Publisher
Springer Netherlands
Published in
Cellular Oncology / Issue 6/2015
Print ISSN: 2211-3428
Electronic ISSN: 2211-3436
DOI
https://doi.org/10.1007/s13402-015-0240-x

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